TMCO1 is a novel target for cancer chemotherapy

Transmembrane and coiled-coil domains 1 (TMCO1) is a protein of 22 KDa highly conserved in amino acid sequence among mammalian species and functions as an endoplasmic reticulum (ER) Ca2+load-activated Ca2+channel. Homozygous frameshift mutation in TMCO1 causes distinctive craniofacial dysmorphism, skeletal anomalies, and mental retardation. However, its physiological functions are largely unknown. In this study, we found that TMCO1 was co-localized with microtubules as determined by immunohistostaining and a co-sedimentation assay. Interestingly, TMCO1 was highly expressed in the invasive front of high grade lung cancer and metastatic cancer cells of clinical specimens. To further investigate the biological role of TMCO1 in lung cancer, we knocked it down in A549 cells, a human lung adenocarcinoma cell line, by using shRNA lentiviral particles. Disruption of TMCO1 in the cells resulted in delayed microtubule polymerization and remarkably increased acetylation of -tubulin. In addition, A549 cells lacking of TMCO1 grew significantly slower than the control cells. Taken together, our findings suggest that TMCO1 may be a therapeutic target for lung cancer treatment.https://engagedscholarship.csuohio.edu/u_poster_2018/1031/thumbnail.jp

Weikangning Therapy in Functional Dyspepsia and the Protective Role of Nrf2

Functional dyspepsia (FD) is a non-organic gastro-intestinal disorder that has a marked negative impact on quality of life. Compared with conventional pharmacological therapies, the traditional Chinese medicine weikangning (WKN) is a safe and effective treatment for FD. The present study aimed to determine the molecular mechanisms underlying the efficacy of WKN. The effect of different concentrations of WKN on the proliferation of the human gastric mucosal epithelial cell line GES-1 was assessed. The optimal WKN concentration to promote cell proliferation was determined, and this concentration was used to examine the effect of WKN compared with a domperidone-treated positive control group on the antioxidant capacity of GES-1 cells. The effect of WKN treatment on the growth and antioxidant activity of GES-1 cells was also assessed following nuclear factor erythroid 2 like 2 (Nrf2) knockdown. The optimal WKN dose for promoting cell growth was determined to be 0.025 mg/ml; at this concentra-tion the expression of the antioxidant proteins glutathione S-transferase P and superoxide dismutase 2 (SOD2) were significantly elevated (

Cobalt(II) Diphenylazodioxide Complexes Induce Apoptosis in SK-HEP-1 Cells

The cobalt(II) complex salts [Co(bpy)(az)2](PF6)2 and [Co(az)4](PF6), each bearing the unusual cis-N,N\u27-diphenylazodioxide ligand, were both screened as possible anticancer agents against SK-HEP-1 liver cancer cells. Both compounds were found to induce substantial apoptosis as an increasing function of concentration and time. Measurement of apoptosis-related proteins indicated that both the extrinsic and intrinsic pathways of apoptosis were activated. The apoptotic activity induced by these salts is not displayed either by simple cobalt(II) salts or complexes or by the free nitrosobenzene ligand. Additionally, these compounds did not induce apoptosis, as assessed by poly(adenosine diphosphate-ribose) polymerase cleavage, in several other cell lines

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1H NMR-based metabolic profiling combined with multivariate data analysis was used to explore the metabolic phenotype of functional dyspepsia (FD) in stressed rats and evaluate the intervention effects of the Chinese medicine Weikangning (WKN). After a 7-day period of model establishment, a 14-day drug administration schedule was conducted in a WKN-treated group of rats, with the model and normal control groups serving as negative controls. Based on 1H NMR spectra of urine and serum from rats, PCA, PLS-DA, and OPLS-DA were performed to identify changing metabolic profiles. According to the key metabolites determined by OPLS-DA, alterations in energy metabolism, stress-related metabolism, and gut microbiota were found in FD model rats after stress stimulation, and these alterations were restored to normal after WKN administration. This study may provide new insights into the relationship between FD and psychological stress and assist in research into the metabolic mechanisms involved in Chinese medicine

Cobalt(II) Diphenylazodioxide Complexes Induce Apoptosis in SK-HEP-1 Cells

The cobalt(II) complex salts [Co(bpy)(az)2](PF6)2 and [Co(az)4](PF6), each bearing the unusual cis-N,N\u27-diphenylazodioxide ligand, were both screened as possible anticancer agents against SK-HEP-1 liver cancer cells. Both compounds were found to induce substantial apoptosis as an increasing function of concentration and time. Measurement of apoptosis-related proteins indicated that both the extrinsic and intrinsic pathways of apoptosis were activated. The apoptotic activity induced by these salts is not displayed either by simple cobalt(II) salts or complexes or by the free nitrosobenzene ligand. Additionally, these compounds did not induce apoptosis, as assessed by poly(adenosine diphosphate-ribose) polymerase cleavage, in several other cell lines

INFLAMMATORY BOWEL DISEASE: CLINICAL FEATURES AND MANIFESTATIONS BEYOND THE BOWEL

Inflammatory bowel disease (IBD) encompasses a spectrum of diseases, with Crohn's disease (CD) and ulcerative colitis (UC) representing the two broadest subtypes of IBD. Multiple extraintestinal manifestations (EIMs) are more frequent in (IBD); 5% –50% of the patients might be affected. The most often implicated sites of manifestations are musculoskeletal and dermatological structures. However, while some symptoms like peripheral arthritis and erythema nodosum correlate with IBD progression, others have their own course of disease like axial arthropathy, gangrenosis of the pioderma and primary sclerosic cholangitis. This review would provide a summary of the most frequent EIMs and their prevalence.                                       Peer Review History: Received 31 May 2020; Revised 7 June; Accepted 4 July, Available online 15 July 2020 Academic Editor: Dr. Muhammad Zahid Iqbal, AIMST University, Malaysia, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Md. Parwez Ahmad, National Medical College, Birgunj, Nepal, [email protected] Dr. George Zhu, Tehran University of Medical Sciences, Tehran, Iran, [email protected]

Effects of myeloperoxidase on inflammatory responses with hypoxia in Citrobacter rodentium‐infectious mice

Abstract Purpose Myeloperoxidase (MPO) has been identified as a mediator in various inflammatory diseases. Bacterial infection of the intestine and hypoxia can both lead to inflammatory responses, but the role of MPO in these phenomena remains unclear. Methods By building the MPO‐/‐ mice, we evaluated relevant inflammatory factors and tissue damage in mice with intestinal Citrobacter rodentium infection and hypoxia. The body weight and excreted microorganisms were monitored. Intestinal tissues were collected 7 days after bacterial infection under hypoxia to undergo haematoxylin‐eosin staining and assess the degree of pathological damage. ELISA assays were performed to quantify the serum levels of TNF‐α, IFN‐γ, IL‐6, and IL‐1β inflammatory cytokines. PCR, WB, and IF assays were conducted to determine the expression of chemokines MCP1, MIP2, and KC in the colon and spleen. Results The C. rodentium infection and hypoxia caused weight loss, intestinal colitis, and splenic inflammatory cells active proliferation in wild‐type mice. MPO deficiency alleviated this phenomenon. MPO‐/‐ mice also displayed a significant decline in bacteria clearing ability. The level of TNF‐α in the serum and spleen was both lower in MPO‐/‐ hypoxia C. rodentium‐infected mice than that in wild‐type mice. The chemokines expression levels of MIP2, KC, and MCP1 in the spleen and colon of each bacterial infected group were significantly increased (p < .05), while in hypoxia, the factors in the spleen and colon were decreased (p < .05). MPO deficiency was found to lower the levels of these chemokines compared with wild‐type mice. Conclusion MPO plays an important role of the inflammatory responses in infectious enteritis and hypoxia in mice, and the loss of MPO may greatly reduce the body's inflammatory responses to fight diseases

Two Chinese patients of sporadic Creutzfeldt–Jacob disease with a S97N mutation in PRNP gene

ABSTRACTWorldwide, 10–15% human prion disease are genetic and inherited, due to the special mutations or insertions in PRNP gene. Herein, we reported two Chinese patients with rapidly progressive dementia who were referred to the national Creutzfeldt–Jacob disease (CJD) surveillance as suspected CJD. Those two patients displayed sporadic CJD (sCJD)-like clinical phenotype, e.g. rapidly progressive dementia, visional and mental problems, sCJD-associated abnormalities in MRI. A missense mutation was identified in one PRNP allele of these two patients, resulting in a change from serine to asparagine at codon 97 (S97N). RT-QuIC of the cerebrospinal fluid samples from those two cases were positive. It indicates that they are very likely to be prion disease

RNase L Is Involved in Liposaccharide-Induced Lung Inflammation

RNase L mediates interferon (IFN) function during viral infection and cell proliferation. Furthermore, the role of RNase L in the regulation of gene expression, cell apoptosis, autophagy, and innate immunity has been well established in the last decade. Tissue distribution reveals that RNase L is highly expressed in the lung and other organs. However, the physiological roles of RNase L in the lung are largely unknown. In this study, we found that polysaccharide (LPS)-induced acute lung injury (ALI) was remarkably intensified in mice deficient in RNase L compared to wild type mice under the same condition. Furthermore, we found that RNase L mediated the TLR4 signaling pathway, and regulated the expression of various pro- and anti-inflammatory genes in the lung tissue and blood. Most importantly, RNase L function in macrophages during LPS stimulation may be independent of the 2-5A system. These findings demonstrate a novel role of RNase L in the immune response via an atypical molecular mechanism